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Biomedical subjects

J C Fenwick

Publications and source records attributed to J C Fenwick.

At least 19 recordsLinked to original sources

Ultraviolet-B radiation effects on antioxidant status and survival in the zebrafish, Brachydanio rerio.

Direct impact of ambient (1.95 W/m2) and subambient doses of UV-B radiation on muscle/skin tissue antioxidant status was assessed in mature zebrafish (Brachydanio rerio). The influence of these doses on hatching success and survival in earlier life stages was also examined. Subambient doses of UV-B radiation in the presence (1.28 W/m2) and absence (1.72 W/m2) of a cellulose acetate filter significantly depressed muscle/skin total glutathione (TGSH) levels compared with controls (0.15 W/m2) and low (0.19 W/m2) UV-B-treated fish after 6 and 12 h cumulative exposure. Ambient UV-B exposure significantly decreased muscle/skin glutathione peroxidase (GPx) activity after a 6 h exposure; activities of glutathione reductase (GR) were unchanged over this exposure period. Superoxide dismutase (SOD) and catalase activities peaked after 6 and 12 h cumulative exposure, respectively, but fell back to control levels by the end of the exposure period. The changes in tissue antioxidant status suggested UV-B-mediated increases in cytosolic superoxide anion radicals (O2-) and hydrogen peroxide (H2O2). This apparent UV-B-mediated increase in oxidative stress is further supported by a significant increase in muscle/skin thiobarbituric acid reactive substances (TBARS). Hatching success of newly fertilized eggs continuously exposed to ambient UV-B was only 2% of the control value. Even at 30 and 50% of ambient UV-B, hatching success was only 80 and 20%, respectively, of the control. Newly hatched larvae exposed to an ambient dose of UV-B, experienced 100% mortality after a 12 h cumulative exposure period. This study supports a major impact of UV-B on both the mature and embryonic zebrafish.

Animals↗

Human cone pigment expressed in transgenic mice yields altered vision.

Genetically driven alterations in the complement of retinal photopigments are fundamental steps in the evolution of vision. We sought to determine how a newly added photopigment might impact vision by studying a transgenic mouse that expresses a human cone photopigment. Electroretinogram (ERG) measurements indicate that the added pigment works well, significantly changing spectral sensitivity without deleteriously affecting the operation of the native cone pigments. Visual capacities of the transgenic mice were established in behavioral tests. The new pigment was found to provide a significant expansion of the spectral range over which mice can perceive light, thus underlining the immediate utility of acquiring a new photopigment. The transgenic mouse also has the receptor basis for a novel color vision capacity, but tests show that potential was not realized. This failure likely reflects limitations in the organizational arrangement of the mouse retina.

Animals↗

The effects of soft-water acclimation on gill structure in the rainbow trout Oncorhynchus mykiss.

Rainbow trout (Oncorhynchus mykiss) were exposed to ion-poor (soft) water to test the hypothesis that naturally induced proliferation of branchial chloride cells causes a thickening of the blood-to-water diffusion barrier. This was achieved by using a combination of scanning and transmission electron-microscopic techniques. Fish were exposed to soft-water conditions ([Na+]= 0.055 mmol l-1, [Cl-] approximately 0.029 mmol 1(-1), [Ca2+] approximately 0.059 mmol 1(-1), and [K+] approximately 0.007 mmol 1(-1)) for 1, 2, and 4 weeks. Marked chloride cell proliferation was evident at all sampling times with an approximate doubling of the gill epithelial surface area covered by chloride cells exposed to the water ("chloride cell fractional area"). The increases in chloride cell fractional area resulted from both increased numbers of cells and expanded apical surfaces of exposed individual cells. As a result of chloride cell proliferation, soft-water exposure was associated with a doubling of the lamellar blood-to-water diffusion distance from 3.26+/-0.08 microM to 6.58+/-0.43 microM as determined from transmission electron micrographs. These data demonstrated a positive correlation between chloride cell fractional area and blood-to-water diffusion distance. We conclude that, in trout, chloride cell proliferation during soft-water exposure, while presumably benefiting ionic regulation, may impair gas transfer owing to the associated thickening of the blood-to-water diffusion barrier.

Acclimatization↗

Does increasing oxygen delivery improve outcome in the critically ill? No.

The strategy of treating critically ill patients by increasing oxygen delivery and consumption to values previously observed among survivors of critical illness (supranormal values) is based on the belief that (1) tissue hypoxia may persist in critically ill patients despite aggressive early resuscitation to traditional endpoints of adequate tissue perfusion and (2) that increasing oxygen delivery can reverse tissue hypoxia. This article addresses the question of whether increasing oxygen delivery improves outcomes in critically ill patients by reviewing the relationship between whole-body oxygen delivery and consumption and by critically examining the randomized controlled trials that have increased oxygen delivery to supranormal values.

Cell Hypoxia↗

N-terminal and C-terminal fragments of the hormone stanniocalcin show differential effects in eels.

The effects of an N-terminal, a C-terminal, and a mid-fragment of stanniocalcin, the primary hypocalcemic hormone in fish, on plasma total and free (ionic) calcium levels and whole animal calcium influx were tested in eels. Both the N- and the C-terminal fragments were hypocalcemic, causing 18 and 12% reduction in plasma calcium in stanniectomized eels, respectively. With both fragments the hypocalcemic action is transient. The hypocalcemia caused by the C-terminal fragment, although more rapid, is not as pronounced as the hypocalcemic action of the N-terminal fragment. Only the C-terminal fragment reduced calcium influx. The hypocalcemic activity of the C-terminal fragment then can be explained by its effect on calcium influx. The N-terminal fragment appears to function in a different manner. The mid-fragment has no effect on plasma calcium or calcium influx. The different parts of the hormone are concluded to have different effects.

Anguilla↗

A passive immunization technique against the teleost hypocalcemic hormone stanniocalcin provides evidence for the cholinergic control of stanniocalcin release and the conserved nature of the molecule.

An in vivo bioassay based on 45Ca uptake from the ambient medium was used to test the efficacy of serum from rabbits immunized against trout stanniocalcin to passively immunize trout, tilapia, American eel, and guppy against endogenous stanniocalcin. The passive immunization was effective in all species. The fact that this procedure worked under both homologous and heterologous conditions, and in fish from different taxonomic infradivisions, is consistent with the view that the stanniocalcins in the four species examined share common antigenic determinants. The trout stanniocalcin antiserum had no effect on whole body calcium uptake (inCa2+) in stanniectomized eels, indicating that the effect of the antiserum was dependent on the presence of functional Stannius corpuscles. The technique was then used to show that the inhibitory effects that calcium loading and the injection of the cholinoreceptor agonist carbachol have on inCa2+ probably involve a catecholamine-induced release of endogenous stanniocalcin from the Stannius corpuscles.

Anguilla↗

Acute quadriparesis in an asthmatic treated with atracurium.

An 18-yr-old male asthmatic was paralyzed with atracurium for a period of seven days to facilitate mechanical pulmonary ventilation. After withdrawal of the muscle relaxant, train-of-four neuromuscular monitoring demonstrated rapid recovery of normal function. Three days later he developed acute quadriparesis without respiratory compromise. Electrophysiological studies showed normal conduction velocities, low compound muscle action potential amplitudes and evidence of denervation. Most cases of post-ventilatory weakness in the ICU involve the use of vecuronium and pancuronium. It has been suggested that the steroid nucleus in these muscle relaxants may be responsible. Our patient developed generalised weakness after treatment with atracurium, a benzylisoquinolinium muscle relaxant. Thus, it appears that the steroid nucleus of vecuronium and pancuronium is not essential in causing post-ventilatory weakness.

Action Potentials↗

Blood transfusion as a cause of leucocytosis in critically ill patients.

The diagnosis of infection in the intensive care unit is confounded by the presence of non-infectious causes of leucocytosis. Unless such causes are recognised, time and effort will be spent on unnecessary investigations and treatments. In a prospective study we have shown that the transfusion of blood frequently (45/50 patients) causes an acute leucocytosis in such patients. This effect was not seen in 8 patients who received plasma. Blood transfusion should be added to the list of non-infectious causes of leucocytosis in the critically ill.

Adult↗

Cholinergic control of stanniocalcin release in the rainbow trout, Oncorhynchus mykiss, and the American eel, Anguilla rostrata.

An in vivo whole animal 45Ca influx bioassay was used to study the cholinergic control of the release of stanniocalcin (STC) in the rainbow trout (Oncorhynchus mykiss) and the American eel (Anguilla rostrata). In both species calcium influx (JinCa2+) was lowered in response to hypercalcemia induced by intravascular (trout) or intraperitoneal (eel) injections of CaCl2. In trout, this response was blocked by the cholinergic antagonist atropine (0.25 mumol kg-1) and mimicked by the cholinoceptor agonist carbachol (0.25 mumol kg-1). These observations are consistent with a cholinergic stimulation of STC release in response to hypercalcemia in trout. In eels, pretreatment with atropine did not block the lowering of JinCa2+ in response to hypercalcemia. This suggests that cholinergic stimulation is not obligatory for stanniocalcin release in eels. However, carbachol treatment did elicit STC release as revealed by the lowering of JinCa2+. This response to carbachol was not observed in stanniectomized eels. Thus, in the American eel it appears that there is a potential for cholinergic control of STC release but that other factors such as the local plasma calcium concentration may also be involved, at least in response to severe acute hypercalcemia.

Anguilla↗

Stimulation of calcium efflux from the hagfish, Eptatretus cirrhatus, gill pouch by an extract of corpuscles of Stannius from an eel (Anguilla dieffenbachii): teleostei.

A factor present in the homogenate of the corpuscles of Stannius from a teleost, the longfin eel Anguilla dieffenbachii, showed calcitropic effects in an agnathan, the hagfish Eptatretus cirrhatus. This factor greatly increased calcium efflux from an isolated perfused gill pouch preparation and had no effect on calcium influx. Hagfish regulated plasma total calcium at a concentration which was about 50% of that of the ambient seawater. Intact hagfish had rates of calcium influx and efflux which were similar to those recorded in teleosts. Hagfish are thus similar to teleosts to the extent that they can and do maintain a plasma calcium concentration which is quite different from that of the ambient medium. They also resemble teleosts in that transepithelial calcium fluxes across the hagfish gill pouches respond to extracts of Stannius corpuscles. Hagfish, however, are quite unlike teleosts in that the Stannius corpuscle extract stimulates calcium efflux rather than inhibiting calcium influx.

Anguilla↗

Identification of the critical oxygen delivery for anaerobic metabolism in critically ill septic and nonseptic humans.

OBJECTIVES: To determine the critical oxygen delivery threshold for anaerobic metabolism and to compare its value between septic and nonseptic critically ill patients. DESIGN: Cohort analytic study, consecutive sample. SETTING: Two tertiary care medical and surgical intensive care units in university hospitals. PATIENTS: Nine septic and nine nonseptic critically ill humans. A diagnosis of sepsis was established by the presence of sepsis syndrome, positive cultures obtained within 48 hours of study, and autopsy evidence of a source of infection. METHODS AND INTERVENTIONS: The O2 consumption (determined by indirect calorimetry), O2 delivery (calculated from the Fick equation), and concentration of arterial plasma lactate were simultaneously determined at 5- to 20-minute intervals while life support was discontinued. MAIN OUTCOME MEASURES: Critical O2 delivery, critical O2 extraction ratio, and maximal O2 extraction ratio. RESULTS: In all septic and eight nonseptic patients, O2 delivery and O2 consumption displayed a biphasic relationship over the range of O2 delivery studied. There were no differences in critical O2 delivery threshold (3.8 +/- 1.5 vs 4.5 +/- 1.3 mL.min-1 x kg-1; P > .28), critical O2 extraction ratio (0.61 +/- 0.05 vs 0.59 +/- 0.16; P > .64), and maximal O2 extraction ratio (0.74 +/- 0.08 vs 0.80 +/- 0.11; P > .29) between septic and nonseptic patients. These data have greater than 90% power to detect a difference of 2 mL.min-1 x kg-1 in the critical O2 delivery and 0.1 in the critical and maximal O2 extraction ratios between the septic and nonseptic groups. CONCLUSIONS: The critical O2 delivery for anaerobic metabolism was identified from the biphasic relationship between O2 delivery and O2 consumption in individual humans. The critical O2 delivery is considerably lower than previously reported in humans with the use of pooled group data. Sepsis does not alter the critical O2 delivery for anaerobic metabolism or tissue O2 extraction ability. Interventions to increase O2 delivery to supranormal levels in critically ill humans in the hope of increasing O2 consumption may be inappropriate.

Adult↗

A C-terminal fragment of the hormone stanniocalcin is bioactive in eels.

An in vivo eel bioassay based on 45Ca uptake from the ambient medium was used to compare the activity of native trout and American eel stanniocalcin (STC) with that of a synthetic C-terminal fragment (AA 202-231; peptide W) of Australian eel STC. Qualitatively, the action of peptide W resembled that of purified native rainbow trout (Oncorhynchus mykiss) STC as well as fresh extracts of American eel Stannius corpuscles in that they all inhibited whole animal Ca2+ influx. This inhibition was observed in both intact and stanniectomized eels regardless of whether the eels were exhibiting high or low initial calcium uptake rates. These observations suggest that peptide W activates eel gill STC receptors. Further, as peptide W was previously reported to stimulate Ca2+ influx in intact rainbow trout fry, the present data provides evidence for a difference in the way this fragment functions in various species.

Anguilla↗

The diagnostic utility of contrast echocardiography in patients with refractory hypoxemia.

Three illustrative cases of refractory hypoxemia in adults are presented. In two cases contrast echocardiography was invaluable in establishing the diagnosis of a true anatomic right to left shunt, as well as in localizing the shunt to an intracardiac or extracardiac site. In the third case true anatomic right to left shunt was excluded by means of contrast echocardiography. The pathophysiology of hypoxemia is discussed with emphasis on the potential diagnostic utility of contrast echocardiology in patients with refractory hypoxemia. A diagnostic flow chart is proposed.

Adult↗

Oxygen consumption is independent of increases in oxygen delivery by dobutamine in septic patients who have normal or increased plasma lactate.

We asked whether the relationship between oxygen delivery and oxygen consumption is different between patients who have sepsis and normal (n = 6) or increased (n = 8) concentrations of plasma lactate. We determined oxygen consumption using analysis of respiratory gases while increasing oxygen delivery using a dobutamine infusion. The relationship between oxygen delivery and consumption was y = 124 + 0.043 * x in the normal lactate group and y = 131 - 0.003 * x in the high lactate group (95% CI for differences in slopes, -0.003 to 0.096; p < or = 0.05 for slope, normal versus high lactate). In the normal lactate group, direct oxygen consumption increased by only 8 +/- 6 ml/min/m2 after dobutamine infusion (from 144 +/- 26 to 153 +/- 22 ml/min/m2, p < or = 0.02) despite an average increase of 220 +/- 80 ml/min/m2 in oxygen delivery (from 446 +/- 91 to 666 +/- 90 ml/min/m2, p < or = 0.01). The oxygen extraction ratio fell from 0.27 +/- 0.03 to 0.21 +/- 0.02 after dobutamine (p < or = 0.017). In the high lactate group, direct oxygen consumption decreased by 1 +/- 6 ml/min/m2 after dobutamine (from 131 +/- 33 to 130 +/- 35 ml/min/m2, p > 0.60) despite an average increase of 168 +/- 138 ml/min/m2 in oxygen delivery (from 467 +/- 194 to 635 +/- 300 ml/min/m2, p < or = 0.01). The oxygen extraction ratio fell from 0.30 +/- 0.14 to 0.26 +/- 0.12 after dobutamine (p < or = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of stanniectomy and experimental hypercalcemia on plasma calcium levels and calcium influx in American eels, Anguilla rostrata, LeSueur.

Intraperitoneal injection of CaCl2 in intact, sham-stanniectomized, and stanniectomized American eels, Anguilla rostrata (LeSueur), resulted in a rapid elevation of plasma calcium level which was more marked and of longer duration in the stanniectomized eels. The same treatment reduced whole body calcium influx (JinCa2+) in the intact and sham-stanniectomized groups for the first but not the second of two 4 hr flux periods. The same treatment did not affect JinCa2+ in the stanniectomized eels. We conclude that calcium loading in eels with intact stannius corpuscles (CS) results in the release of a CS hormone (stanniocalcin) which inhibits the uptake of calcium from the environment and that this facilitates the return to normocalcemia. These data provide direct evidence for a relationship between stanniocalcin release in vivo and a hypocalcemic response and the first evidence concerning the functional turnover time of this hormone.

Anguilla↗

Oxygen consumption is independent of changes in oxygen delivery in severe adult respiratory distress syndrome.

We asked whether oxygen consumption is dependent on oxygen delivery in 17 patients who had severe adult respiratory distress syndrome (ARDS), 10 of whom had increased concentrations of plasma lactate. We determined oxygen consumption using analysis of respiratory gases while increasing oxygen delivery using blood transfusion. Oxygen consumption did not change after transfusion (from 227 +/- 83 to 225 +/- 82 ml/min, p less than or equal to 0.38). Oxygen delivery increased from 1,043 +/- 468 ml/min (24%, p less than or equal to 0.001). Even in the 10 patients who had increased concentration of plasma lactate and metabolic acidosis, oxygen consumption remained constant after increasing oxygen delivery (pretransfusion, 224 +/- 101 ml/min; post-transfusion, 225 +/- 99 ml/min; p less than or equal to 0.83). These data have more than 99% power of detecting a change in oxygen consumption of 20 ml/min after transfusion. Therefore, we conclude that directly measured oxygen consumption remains constant and independent of increases in oxygen delivery in our patients with severe ARDS. Because simultaneously determined oxygen consumption calculated from variables shared with the calculation of oxygen delivery yielded a dependent relationship, we speculate that finding dependence of calculated oxygen consumption on oxygen delivery may be the result of methodologic error.

Aged↗